Periodontal disease is an inflammatory disorder of the supporting tissue of teeth. Without control, chronic inflammatory condition associated with periodontal disease will destroy tissue supporting teeth and eventually result in teeth loss.
Attempts have been made to alleviate periodontal disease using chemical agents. For example, U.S Pat. No. 4,789,662 to Thomas-Leurquin et al. discloses a pharmaceutical composition including collagen and a chlorhexidine antiseptic and anti-inflammatory substance. However, the traditional mode of prevention and treatment of periodontal disease has centered on maintaining good oral hygiene. This consists of, among other things, removal of dental plaque which is considered to be the etiological cause of dental caries and periodontal disease. Dental plaque consists of microbial masses which deliver a stream of enzymes, endotoxins and exotoxins onto gingival and marginal periodontal tissue leading to inflammation. The resulting inflammatory response triggers a series of catabolic processes. Specifically, as tissue reacts to protect itself from these toxic assaults, complex changes occur in the immune system in the function of osteoclasts, in the activity of lymphocytes in the blood streams, and in other bodily defenses. These changes and complement activation lead to increased prostaglandin formation at the inflammation site.
Prostaglandin, and related compounds, are principally formed by body cells at the site of tissue injury by a process known as arachidonic acid cascade This process occurs when essential fatty acids, especially linoleic acid, are enzymatically converted into arachidonic acid, which in turn is further metabolized through either the cyclooxygenase or lipoxygenase pathways to prostaglandins (PGS).
Prostaglandins, particularly prostaglandin-E.sub.2 (PGE.sub.2), have been implicated as components of the inflammatory reaction. Goodson et al., Prostaglandins, 6, 81-85 (1984) and El Attar et al., J. Periodontal, 52, 16-19 (1981) demonstrated that PGE.sub.2 levels are elevated in inflamed gingiva when compared to normal gingiva. Offenbacher et al., J. Periodont. Res., 21, 101-112 (1986) demonstrated that extremely high levels of PGE.sub.2 are present at periodontal sites of active attachment loss and low at sites which are in remission, i.e. there is no longitudinal attachment loss. The PGE.sub.2 level in diseased tissue approximates 1 uM (Offenbacher et al., J. Periodon. Res. 19, 1-13 (1984)) which is a pharmacologically active concentration when tested in various model systems to induce vasodilation, bone resorption and other pro-inflammatory responses.
Despite this evidence regarding the key role of PGE.sub.2 in the pathogenesis of periodontal disease, there has been substantially little appreciation of the use of drugs which inhibit PGE.sub.2 synthesis in an attempt to retard or prevent periodontal tissue destruction.